Department of Medical Oncology, Institut Bergonié, Bordeaux, France.
University Bordeaux, Inserm, Bordeaux Population Health Research Center, Epicene Team, UMR 1219, F-33000 Bordeaux, France; Inserm CIC1401, Clinical and Epidemiological Research Unit, Institut Bergonié, Comprehensive Cancer Center, F-33000 Bordeaux, France.
Eur J Cancer. 2022 Nov;175:43-53. doi: 10.1016/j.ejca.2022.08.014. Epub 2022 Sep 8.
Recent studies suggest improvements in response to salvage chemotherapy (CT) after immune checkpoint inhibitors (ICIs) in several types of cancer. Our objective was to assess the efficacy of chemotherapy re-challenge after ICI, compared with second-line chemotherapy without previous ICI in patients with locally advanced or metastatic urothelial carcinoma (la/mUC).
In this multicentre retrospective study, we included all patients with la/mUC initiating second or third-line chemotherapy from January 2015 to June 2020. We compared patients treated with second-line chemotherapy without previous ICI (CT2) and patients treated with third-line chemotherapy after ICI (CT3). The primary end-point was objective response rate (ORR) in CT3 compared with CT2. Secondary end-points included progression-free survival (PFS) and toxicities.
Overall, 553 patients were included. ORRs were 31.0% (95% CI, 26.5 to 35.5) and 29.2% (95% CI, 21.9 to 36.6), respectively, in CT2 and CT3, with no statistically significant differences (P = 0.62). In subgroup analyses, no differences in ORR were observed by Bellmunt risk group, type of chemotherapy (platinum or taxanes), duration of response to first-platinum-based chemotherapy (< or ≥ 12 months) or FGFR-status. Median PFS was 4.6 months (95% CI, 3.9 to 5.1) and 4.9 months (95% CI, 4.1 to 5.5) in CT2 and CT3, respectively, and grade 3-4 hematologic toxicity occurred in 35.0% and 22.4% of patients.
This large multicentre retrospective study provides clinically relevant real-world data. Chemotherapy re-challenge after ICI in la/mUC achieves ORR and PFS comparable with those obtained in CT2 with an acceptable safety profile. These updated results offer more promising outcomes than historically reported with second-line chemotherapy data.
最近的研究表明，在几种类型的癌症中，免疫检查点抑制剂（ICI）后挽救性化疗（CT）的反应有所改善。我们的目的是评估ICI 后 CT 再挑战的疗效，与既往未接受 ICI 的二线化疗（CT2）相比，在局部晚期或转移性尿路上皮癌（la/mUC）患者中。
在这项多中心回顾性研究中，我们纳入了 2015 年 1 月至 2020 年 6 月期间开始二线或三线化疗的所有 la/mUC 患者。我们比较了未接受既往 ICI 的二线化疗（CT2）和 ICI 后三线化疗（CT3）的患者。主要终点是 CT3 与 CT2 相比的客观缓解率（ORR）。次要终点包括无进展生存期（PFS）和毒性。
总体而言，共纳入 553 例患者。CT2 和 CT3 的 ORR 分别为 31.0%（95%CI，26.5-35.5）和 29.2%（95%CI，21.9-36.6），无统计学差异（P=0.62）。亚组分析显示，Bellmunt 风险组、化疗类型（铂类或紫杉类）、首次基于铂类化疗的缓解持续时间（<12 个月或≥12 个月）或 FGFR 状态对 ORR 无差异。CT2 和 CT3 的中位 PFS 分别为 4.6 个月（95%CI，3.9-5.1）和 4.9 个月（95%CI，4.1-5.5），35.0%和 22.4%的患者发生 3-4 级血液学毒性。
这项大型多中心回顾性研究提供了具有临床意义的真实世界数据。ICI 后 la/mUC 的化疗再挑战可获得与 CT2 相当的 ORR 和 PFS，且安全性可接受。这些更新的结果比历史上报道的二线化疗数据提供了更有希望的结果。
